u.c. 


UC" 


777 


MELLON    LECTURE 

(UNDER  THE  AUSPICES  OF  THE  SOCIETY  FOR  BIOLOGICAL   RESEARCH) 

UNIVERSITY  OF  PITTSBURGH 
SCHOOL  OF  MEDICINE 


SEVENTH    LECTURE 

INTERPRETATIONS    OF    THE    INITIAL    PHASES 
OF    THE    ELECTROCARDIOGRAM    WITH 
SPECIAL    REFERENCE    TO    THE 
THEORY  OF  "LIMITED  POTEN- 
TIAL DIFFERENCES" 


BY 


SIR  THOMAS  LEWIS,  M.D.,  F.R.C.P. 


1922 


INTERPRETATIONS    OF    THE    INITIAL     PHASES 
OF  THE   ELECTROCARDIOGRAM  WITH 
SPECIAL    REFERENCE    TO    THE 
THEORY  OF  "LIMITED  POTEN- 
TIAL   DIFFERENCES" 


) 

SIR  THOMAS/LEWIS,  M.D.,  F.R.C.P. 


LONDON 


SEVENTH     MELLON     LECTURE,     DELIVERED     BEFORE     THE 

SOCIETY  FOR  BIOLOGICAL  RESEARCH,  UNIVERSITY  OF 

PITTSBURGH    SCHOOL    OF    MEDICINE,  MAY   8,   1922. 


MELLON     LECTURE 

(UNDER  THE  AUSPICES  OF  THE  SOCIETY  FOR   BIOLOGICAL    RESEARCH) 

UNIVERSITY  OF  PITTSBURGH 
SCHOOL  OF  MEDICINE 


SEVENTH    LECTURE 

INTERPRETATIONS    OF    THE    INITIAL    PHASES 
OF    THE    ELECTROCARDIOGRAM    WITH 
SPECIAL    REFERENCE    TO    THE 
THEORY  OF  "LIMITED  POTEN- 
TIAL DIFFERENCES" 


BY 


SIR  THOMAS  LEWIS,  M.D.,  F.R.C.P. 


1922 


INTERPRETATIONS   OF   THE   INITIAL   PHASES    OF  THE 
ELECTROCARDIOGRAM    WITH    SPECIAL    REFER- 
ENCE   TO    THE    THEORY    OF    "LIMITED 
POTENTIAL    DIFFERENCES"  * 

SIR    THOMAS     LEWIS,    M.D.,    F.R.C.P. 

LONDON 

The  subject  chosen  for  this  lecture  is  one  on  which  much  has  been 
written  in  recent  years,  but  upon  which  there  is  still  no  complete  con- 
sensus of  opinion.  In  a  review x  written  about  three  years  ago  I 
attempted  to  explain  the  constitution  of  the  electrocardiogram  on  a 
new  basis  and  put  forward  views  of  a  novel  kind.  These  views  have 
been  accepted  by  a  number  of  workers ;  from  other  workers  they  have 
received  criticism,  publicly  or  privately  expressed.  The  lack  of  uniform 
conclusions,  I  think,  results  largely  from  misunderstandings,  such  mis- 
understandings as  may  be  expected  to  arise  when  the  subject  discussed 
is  not  only  intricate  but  concerned  with  the  ultimate  processes  of 
cellular  activity  and  its  manifestations.  In  studying  the  electrocardiogram 
we  attempt  to  explain  its  general  deflections  in  rational  terms,  yet  the 
terms  which  we  are  forced  to  employ  are  terms  which  refer  to  intimate 
and  intangible  effects  of  cellular  physics  and  chemistry.  Although,  as 
may  be  acknowledged  at  once,  I  have  experienced  recurring  difficulty  in 
my  attempts  clearly  to  conceive  the  manner  in  which  the  electrical 
events  are  related  to  events  in  the  muscle;  yet  the  conception  at  which 
I  arrived  some  few  years  ago  and  which  is  now  reconsidered  in  the 
light  of  recent  discussion  and  observation  has  not  altered  fundamentally, 
though  it  may,  perhaps,  have  grown  a  little  clearer  during  the  interval. 
In  attempting  a  more  distinct  statement  of  the  case  it  seems  desirable  to 
state  that  while  I  refuse  to  stand  committed,  once  and  for  all.  to  these 
views,  yet  our  present  knowledge  does  seem  to  necessitate  movement 
from  the  older  hypotheses  in  some  such  direction  as  will  be  indicated. 

In  discussing  the  question  before  us  one  rule  stands  out  as  paramount 
in  importance ;  the  facts  and  the  hypotheses  must  be  divided  from  each 
other  as  scrupulously  as  possible.  Hypothesis  cannot  be  avoided,  per- 


*  Seventh  Mellon  lecture. 

*  Working  on  behalf  of  the  British  Medical  Research  Council  at  University 
College  Hospital  Medical   School,  London.     Delivered  before  the  Society  for 
Biological    Research,    School    of   Medicine,    University   of   Pittsburgh,   May   8, 
1922. 

1.  Lewis:    The    Mechanism    and    Graphic    Registration    of   the    Heart    Beat, 
London,  1920. 


SIR    THOMAS     LEWIS 


haps  never  will  be  avoided,  in  a  full  consideration  of  our  problem,  and 
it  would  be  presumptuous  if  my  views  were  brought  before  you  as 
views  approaching  to  a  final  solution.  Nevertheless,  by  carefully  weigh- 
ing our  present  knowledge,  certain  final  statements  may  be  made,  certain 
statements  may  be  denied,  and  we  can  bring  our  conceptions  a  step 


—  A 


Fig.    1. — Diagrams,    illustrating  the   potential   differences    in   simple   muscle 
strips,  activated  at  one  end. 

nearer  clarity  and  truth.  Of  one  thing  I  feel  sure,  namely,  that  a  close 
consideration  of  the  views  expressed,  and  further  observations  tending 
either  to  support  or  to  destroy  them,  will  prove  fruitful. 

In  considering  the  meaning  of  the  electrocardiogram,  we  have  all 
started  from  a  common  basis.  By  common  consent,  if  you  place  two 
leading-off  electrodes  directly  on  the  two  ends  of  a  narrow  strip  of 


ELECTROCARDIOGRAM  7 

uninjured  muscle  (Fig.  1  A)  and  now  stimulate  the  muscle  to  contract 
in  the  region  of  one  contact,  the  galvanometer  shows  the  development 
of  a  difference  in  potential  between  the  two  contacts,  that  which  lies 
at  the  point  stimulated  (Z)  becoming  negative  relative  to  its  fellow  (C). 
The  galvanometer  shows  us  that  an  electromotive  force  is  developed 
between  these  two  points ;  current  flows  from  one  to  the  other  through 
the  muscle  and  through  the  galvanometer.  This  experiment,  easily 
performed,  has.  been  carried  out  by  very  numerous  observers  with 
uniform  results;  the  same  event  is  witnessed  whether  voluntary  or 
cardiac  muscle  is  used,  but  it  is  the  last  only  which  I  shall  ask  you  to 
hold  in  mind  during  this  lecture,  for  it  is  on  cardiac  muscle  alone  that  I 
feel  competent  to  speak,  and  in  respect  of  which  alone  I  shall  draw  my 
conclusions.  It  is  on  this  experiment  that  the  conclusion,  which  we 
have  all  accepted,  is  based,  namely,  that  cardiac  muscle  entering  the 
active  state  shows  relative  negativity  to  muscle  which  is  inactive.  But 
although  this  observation  is  easy  to  confirm,  and  although  the  con- 
clusion derived  from  it  does  not  seem  open  to  question,  I  believe  that  it 
often  gives  rise  to  misconception  when  the  meaning  of  the  electro- 
cardiogram is  considered  in  the  light  of  it. 

The  way  in  which  the  chief  misconceptions  arise  I  will  endeavor 
to  explain  ultimately.  Meanwhile,  it  should  be  remarked  that  in  the 
simple  experiment  described  the  electrodes  are  placed  against  very  small 
areas  of  the  muscle  strip;  this  method  of  leading  chiefly  signals  the 
events  which  occur  at  the  ends  of  the  muscle,  rather  than  the  events  in 
its  whole  length.  Further,  it  is  to  be  noted  that  when  a  difference  of 
potential  arises  between  the  two  ends  as  a  result  of  activity  of  one  end, 
the  current  flow  is  necessarily  confined  to  the  line  of  the  muscle;  for 
the  muscle  is  isolated.  The  line  of  the  muscle  represents  the  line  of 
the  electrical  axis,  or  the  line  of  maximal  potential  difference. 

Let  us  now  take  a  second  example  (Fig.  IB),  one  which,  in  the 
simple  form  illustrated,  is  theoretical,  but  one  which  would  be  more 
comparable  to  the  experiment  of  electrocardiography.  Imagine  a  strip 
of  cardiac  muscle  completely  embedded  in  a  moist  conducting  sub- 
stance, and  that  our  contacts  are  placed,  not  immediately  on  the  ends 
of  the  strip,  but  on  the  substance  in  which  the  muscle  lies  embedded. 
So  they  lie  in  human  electrocardiography.  If  now  the  muscle  end  1 
becomes  active,  the  galvanometer  will  again  record  current  flow.  The 
muscle  end  1  we  know  becomes  relatively  negative  to  the  muscle  end  3 ; 
the  contacts  Z  and  C  will  no  doubt  reflect  this  change.  If  you  wish 
to  do  so  you  may  regard  the  contacts  as  prolonged  through  the  medium 
in  which  the  muscle  is  embedded,  to  the  nearest  points  of  the  muscle, 
i.  e.,  to  the  original  ends  1  and  3.  There  is  this  contact,  but  it  is  not 
the  sole  contact,  for  our  electrodes  are  now  connected,  not  only  to 
the  ends  of  the  muscle,  but  to  its  whole  surface.  This  difference 


8  SIR    THOMAS    LEWIS 

between  the  two  methods  of  leading  off  should  not  influence  the  direction 
of  the  first  potential  difference  exhibited  by  contact  C  and  Z,  when,  as 
in  our  illustration,  we  are  dealing  with  a  straight  and  narrow  strip  of 
muscle  lying  in  one  line  between  the  contacts ;  but  as  we  shall  see,  it 
becomes  of  consequence  when  the  relation  of  muscle  to  contacts  is 
altered.  A  second  difference  between  the  two  methods  of  leading  off  is 
also  to  be  noted.  When,  in  the  last  experiment,  the  muscle  is  embedded 
in  a  conducting  substance,  the  current  flows  not  only  through  the  muscle 
and  galvanometer ;  it  flows  through  the  surrounding  medium.  In  other 
words,  we  have  introduced  a  series  of  shunts  along  the  borders  of  the 
muscle  and  these  decrease  the  amount  of  current  flowing  through  the 
galvanometer.  While  we  may  expect  the  movement  of  the  galvano- 
metric  recorder  to  maintain  its  original  direction  (contact  Z  showing 
relative  negativity  to  contact  C),  we  may  not  expect  its  movement  to  be 
so  considerable. 

I  emphasize  the  fact  that  the  comparison  made  is  between  an  actual 
experiment  (Fig.  1  A)  and  a  theoretical  experiment  (Fig.  IB).  The 
actual  events  in  the  second  experiment  (Fig.  IB)  have,  I  think,  not  been 
recorded,  though  there  is  sufficient  evidence  based  on  observation  of  a 
less  direct  kind  to  convince  us  that  the  curves  obtained  in  the  first  and 
second  experiment  will  have  the  same  general  form  in  their  initial  phase. 
That  there  will  be  this  smilarity  is,  I  think,  generally  recognized ;  it  is 
not  a  matter  in  dispute.  But  this  conception  is  apt  to  lead  up  to  a 
second,  namely,  that  curves  taken  by  the  two  methods  are  built  up  in 
identical  fashions ;  and  that  the  two  methods  of  leading  will  in  all 
circumstances  yield  similar  results.  They  may  do  so  when  a  simple  and 
narrow  strip  of  muscle  is  placed  in  line  with  the  leading  off  contacts; 
but  they  do  not,  I  believe,  in  all  circumstances.  Suppose  that  the 
unembedded  muscle  is  bent  on  itself  at  one  end  and  that  the  contacts  are 
placed  at  2  and  3  (Fig.  1C).  Again,  there  will  be  agreement  as  to  the 
effect  produced.  Soon  after  1  is  stimulated,  a  current  will  flow  through 
the  galvanometer  in  the  original  direction,  indicating  that  contact  Z 
has  become  relatively  negative  to  C,  This  change  is  set  up  when  the 
muscle  on  which  contact  Z  lies  becomes  active.  It  is  not  produced  by 
activity  of  the  muscle  strip  between  1  and  2 ;  activity  in  this  portion  of 
the  muscle  has  no  material  effect  since  the  free  end  1  is  not  connected 
to  the  leading  off  contact  C.  This  illustration  serves  to  emphasize 
the  fact  that  when  contacts  are  placed  directly  on  the  muscle,  that  it  is 
an  event  occurring  in  the  muscle  immediately  under  the  proximal  con- 
tact which  is  responsible  for  the  first  swing  of  the  recording  instrument. 

We  come  next  to  the  fourth  and  crucial  example,  the  muscle  bent  on 
itself  and  embedded  (Fig.  ID).  In  these  circumstances  how  will  the 
current  first  flow?  I  have  asked  this  question  of  many  physiologists 


ELECTROCARDIOGRAM  9 

during  the  past  six  years,  and  have  obtained  almost  always  the  reply 
that  the  direction  of  current  flow  will  be  the  same  as  in  the  last  example. 
It  is  said  that  1  will  become  negative  relative  to  3,  and  that  conse- 
quently Z  will  show  negativity  relative  to  C.  Now,  this  reply  is  an 
assumption  ultimately  based  on  the  belief  that  the  two  methods  of  lead- 
ing off  are  sufficiently  similar;  actually  the  experiment  has  not  been 
performed  in  this  simple  form.  For  a  long  while  I  have  felt  unable  to 
accept  this  view  of  what  will  happen.  The  view  is  inconsistent  with 
certain  experiments  which  will  be  described  presently.  The  view  which 
I  put  forward  is  that  relative  negativity  will  first  develop  at  contact  C; 
and  it  will  develop  at  C  because,  when  1  becomes  active,  we  are  leading 
off  from  the  embedded  strip  of  muscle  1  to  2,  and  the  remainder  of  the 
strip  2  to  3  does  not  for  the  moment  concern  us.  It  does  concern  us 
of  course  when  the  excitation  wave  in  traveling  along  the  strip  moves 
into  the  region  between  2  and  3 ;  when  the  wave  in  traveling  has  turned 
the  corner,  Z  will  become  relative  to  C,  the  flow  of  current  becoming 
in  consequence  reversed.  But  for  the  moment  we  shall  do  well  to 
concentrate  attention  on  the  first  phase  of  the  reaction,  for  this  is  in 
dispute. 

The  statement  just  made  in  respect  of  the  first  phase,  brings  us 
I  think  to  the  critical  arguments  of  the  discussion,  namely,  does  the 
prolongation  of  the  strip  from  2  to  3  effect  the  reaction  shown  by  the 
galvanometer  when  1  becomes  active.  The  usual  view  has  been  that  it 
will.  My  own  view  is  that  it  does  not. 

You  may  ask,  why  the  actual  experiment  is  not  performed?  The 
reply  is  that  it  cannot  be  carried  out  in  so  simple  a  fashion  on  cardiac 
muscle  which  is  uninjured,  and  that  if  you  use  injured  muscle,  your 
experiment  is  open,  on  theoretic  grounds,  to  serious  criticism.  But,  as 
I  hope  later  to  show,  the  experiment  can  be  performed  under  somewhat 
more  complex  conditions,  and  that  it  yields  the  results  which  I  anticipate. 

The  argument  turns  as  stated  on  the  influence  or  noninfluence  of  the 
portion  of  muscle  2  to  3,  on  the  initial  electrical  reaction.  According  to 
one  view,  that  which  seems  so  far  to  have  obtained  the  greater  number 
of  direct  or  indirect  supporters,  you  are  to  consider  1  as  relatively 
negative,  and  to  consider  the  whole  of  the  remainder  of  the  muscle 
as  relatively  positive.  This  view  implies  that  in  determining  the  direc- 
tion of  flow,  you  are  to  join  the  center  of  the  active  mass  of  muscle  to 
the  center  of  the  inactive  mass.  According  to  the  other  view,  you  are 
to  consider  the  part  of  the  muscle  which  is  becoming  active  as  relatively 
negative,  and  the  inactive  muscle  in  union  with  it  and  in  its  immediate 
vicinity  as  relatively  positive.  I  put  forward  this  second  view  because 
it  is  consistent  with  and  explains  my  experiments  and  because  so  .far  as 
I  am  aware  it  is  inconsistent  with  no  other  experimental  facts ;  the 
first  view,  though  it  is  admittedly  consistent  with  many  experiments,  is 


10  SIR    THOMAS    LEWIS 

not  consistent  with  all.  For  the  sake  of  brevity  we  may  term  the  first 
hypothesis  that  of  "distributed  potential  differences,"  the  second  that  of 
"limited  potential  differences." 

At  this  point  it  may,  perhaps,  be  appropriate  to  allude  to  my  previous 
review.  You  will  perceive  that,  if  the  hypothesis  of  limited  potential 
differences  is  correct,  the  direction  in  which  the  current  sets  in  the 
muscle  will  be  the  direction  in  which  the  excitation  wave  is  at  that 
moment  traveling,  for  it  will  always  move  from  the  point  which  is 
becoming  active  to  inactive  muscle  in  the  immediate  vicinity  of  the 
latter.  This  association,  which  I  believe  to  be  an  absolutely  constant 
one,2  is  one  on  which  I  have  laid  stress ;  in  doing  so  I  have  tended  to 
imply  that  the  first  is  dependent  on  the  second.  Such  has  not  been  my 
meaning  though  it  has  been  inferred  from  what  has  been,  perhaps,  an 
unfortunate  phraseology,  and  this  inference  is  perhaps  chiefly  respon- 
sible for  misconception  of  my  hypothesis.  To  state  that  the  direction 
which  the  excitation  wave  takes  in  traveling  governs  the  form  of  the 
corresponding  curve,3  cannot  be  considered  fundamentally  sound. 

A  more  correct  expression  would  be  that  both  are  governed  by  one 
series  of  events  in  the  muscle,  and  in  consequence  are  definitely  asso- 
ciated. It  has  been  a  matter  of  descriptive  convenience  to  associate  these 
two  phenomena,  direction  of  movement  and  direction  of  current  flow. 
But  because  the  meaning  may  be  inferred  that  one  is  responsible  for 
the  other,  I  shall  endeavor  to  avoid  this  method  of  description  in  my 
subsequent  remarks. 

Returning  to  the  question  at  issue,  namely,  the  influence  of  outlying 
muscle  on  the  electrical  reaction,  let  us  consider  the  case  of  two  entirely 
separate  masses  of  muscle  (Fig.  IE).  Under  this  arrangement,  if  1 
becomes  active,  the  contacts  at  C  will  become  negative  to  the  contact  Z. 
Here  no  one  argues  that  the  presence  of  the  inactive  muscle  strip  2  to 
3  will  influence  the  result,  it  becomes  part  of  the  moist  substance  in 
which  the  strip  1  and  2  is  embedded.  To  illustrate  this  statement,  take 
the  example  of  complete  heart  block.  When  the  auriculoventricular 
bundle  is  divided  experimentally  or  by  disease,  the  electrocardiogram 
records  the  independent  activities  of  auricle  and  ventricle.  Each  cham- 
ber gives  its  separate  curve,  but  the  curves  of  one  and  the  other  fall  in 


2.  I  would  here  express  the  view  that,  unless  the  conditions  are  very  simple, 
the  direction  in  which  the  current  is  setting  in  a  muscle  strip  as  a  whole  is  not 
to  be  ascertained  with  certainty  from  an  examination  of  two  small  points  of 
contact  on  its  surface  (as  in  Fig.  1A)  ;  but  in  my  view  it  can  be  ascertained  by 
the  method  of  leading  which  Fig.  IB  illustrates.     When   I  say  that  the  asso- 
ciation between  the  set  of  current  and  direction  of  travel  is  constant,  I  wish 
to  refer  to  direction  of  current  as  ascertained  by  the  method  of  indirect  leading 
(method  of  Fig.  IB)  and  by  this  method  only. 

3.  The  phrase  actually  used  in  "The  Mechanism  and  Graphic   Registration 
of  the  Heart  Beat,"  London,  1920.  . 


ELECTROCARDIOGRA  M 


11 


varying  relationship  to  each  other.  It  is  quite  clear  from  such  records 
that  activity  or  inactivity,  partial  or  complete,  in  one  chamber  has  no 
influence  on  the  shape  or  amplitudes  of  the  electrical  currents  derived 
from  the  other  (Fig.  2).  Providing  that  we  are  dealing  with  separate 
masses  of  heart  muscle,  the  electromotive  forces  set  up  in  one  chamber 
are  not  influenced  by  those  set  up  in  the  other.  The  forces  developed 
in  the  two  chambers  find  full  and  individual  expression ;  in  explaining 
such  curves  we  do  not  balance  activity  in  one  chamber  against  inactivity 
in  the  other. 

In  regard,  therefore,  to  the  illustration  (Fig.  IE)  we  are  safe  in 
assuming  that  the  activation  of  strip  1  to  2  at  point  1  will  yield  an 
electromotive  force  having  a  certain  direction  and  amplitude,  indepen- 
dently of  what  is  happening  in  the  strip  2  to  3.  How  does  this  arrange- 
ment of  the  muscle  fibers  differ  from  that  illustrated  by  Figure  ID. 


2ZF 


•fcstc. 


Fig.  2.  Electrocardiograms  from  a  case  of  complete  heart  block,  and  taken 
by  means  of  Leads  I,  II  and  III. 

In  one  respect  only ;  in  the  first  illustration  there  is  functional  union 
between  the  two  strips  at  the  point  2.  If  1  is  stimulated  to  activity  in 
these  two  sets  of  circumstances,  will  the  initial  resultant  swings  of  the 
galvanometer  be  in  opposite  directions ;  will  they  indicate  relative  nega- 
tivity at  Z  in  one  case  and  at  C  in  the  other  ?  According  to  the  hypothe- 
sis of  distributed  potentials  this  will  happen.  But  in  both  instances, 
when  1  becomes  active,  the  strip  2  to  3  is  recognized  to  be  in  a  state 
of  inactivity.  The  distribution  of  potentials  is  the  same  in  both, 
unless  we  are  to  assume  that  when  the  two  strips  are  part  of  one  undi- 
vided piece  of  muscle,  an  active  change  happens  in  strip  2  to  3,  render- 
ing it  relatively  more  positive  to  1.  In  other  words,  if  we  are  to  accept 
the  hypothesis  of  distributed  potentials,  it  is  essential  to  assume  that, 
from  its  initiation,  active  change  produced  by  stimulation  does  not 
confine  itself  to  that  end  of  the  muscle  which  is  stimulated.  I  know  of 


12 


SIR    THOMAS     LEWIS 


Fig.  3  A  and  B. — When  the  heart  is  stimulated  at  its  epicardial  surface  (Fig. 
3B),  contacts  placed  in  line  with  the  point  stimulated  show  first  of  all  an  elec- 
trical relation  which  is  indicated  by  the  large  +  and  —  signs.  This  reaction  of  the 
contacts  is  explained  alternatively  by  the  hypotheses  of  distributed  and  limited 
potential  differences  (see  small  -)-  and  —  signs  of  the  diagram).  In  this  example 
the  distribution  of  potentials  in  the  muscle  and  under  the  contacts  is  consistent, 
irrespective  of  the  hypothesis  chosen.  A,  C  and  D :  The  heart  is  stimulated  at 
its  endocardial  surface  and  the  potential  difference  recorded  by  the  contacts 
is  at  first  in  one  direction  (phase  1)  and  later  becomes  reversed  (phase  2). 
The  supposed  potential  differences  in  the  muscle,  during  the  second  phase,  are 
consistent  with  what  is  found  at  the  contact  points,  irrespective  of  the  hypothesis 
adopted;  but  this  is  not  so  for  the  first  phase;  in  this  the  hypothesis  of  limited 
potential  differences  is  alone  consistent  with  observation. 


ELECTROCARDIOGRA  M 


13 


no  evidence  in  favor  of  such  a  diffused  effect;  on  the  contrary,  the 
argument  based  on  the  fact  that  in  one  instance  we  are  dealing  with  a 
single  piece  of  muscle  and  in  the  other  case  with  separate  pieces  of 
muscle,  though  plausible,  can  be  shown  to  be  unsound.  The  experiment 
of  the  bent  piece  of  muscle  can  be  performed  on  uninjured  heart  muscle. 
It  is  accomplished  as  follows  :  Leading  off  contacts  are  placed  on  a  dog's 
chest  wall  (Fig.  3 A),  the  one  on  the  right  side,  the  other  on  the  left, 
and  the  right  ventricle  is  stimulated  first  on  its  epicardial  surface  at  2, 
and  secondly  on  its  endocardial  surface  at  1,  the  points  stimulated 
being  in  the  same  line  as  the  leading  off  contacts.  It  will  be  obvious 
that,  when  we  stimulate  at  2,  the  excitation  wave  will  move  in  a  general 
direction  in  the  body  from  right  to  left  across  the  heart  (from  2  toward 
3).  It  will  be  equally  obvious  that  if  we  stimulate  at  1  the  excitation 
will  at  first  move  in  a  general  direction  from  1  toward  2,  and  that  a 
little  later  the  general  course  from  2  toward  3  will  be  pursued.  In  the 


\ 


i  \ 


1      ( 

S  i  S 

M 


Fig.  4.  An  example  of  the  findings  of  four  distinct  experiments.  The  lead 
was  from  the  right  chest  wall  (Z  contact)  to  the  left  chest  wall  (C  contact)  and 
the  wall  of  the  right  ventricle  was  stimulated  on  its  epicardial  surface  (right 
hand  record),  and  on  its  endocardial  surface  (left  hand  record).  In  the  last 
case  a  small  pair  of  long  insulated  electrodes  was  introduced  through  a  small 
slit  in  the  wall  of  the  conus  or  through  the  jugular  vein.  The  two  points  of 
stimulation  (inside  and  outside)  lay  no  more  than  0.5  cm.  from  each  other. 
The  curves  differ  in  one  respect,  the  left  hand  curve  begins  with  an  initial 
phase  i  directed  downward,  in  the  right  hand  curve  this  phase  is  directed 
upward.  These  initial  phases  of  the  curves  correspond  to  involvement  of  the 
wall  at  the  point  stimulated  (the  involvement  being  in  opposite  directions  in 
the  two  circumstances).  The  main  deflection  m  is  similar  in  both  curves;  it 
represents  spread  from  right  to  left  in  the  ventricles  as  a  whole.  Curves  of 
this  kind  are  obtained  most  successfully  if  the  lungs  are  well  inflated  so  that 
good  contact  is  maintained  between  the  sides  of  the  heart  and  the  chest  wall. 
The  curves  represent  responses  to  rhythmic  break  shocks  (single  shocks  give 
similar  effects).  The  stimulus  is  recorded  electrically  in  the  top  line.  The  curves 
are  not  distorted  by  the  stimuli,  as  the  time  relations  of  stimulus  and  shock 
show ;  reversal  of  the  direction  in  which  the  stimulus  entered  the  heart  did  not 
affect  the  form  of  the  curves. 


14  SIR    THOMAS    LEWIS 

first  case  the  general  direction  in  the  body  will  be  from  right  to  left 
throughout  the  whole  excitation  of  the  ventricle ;  in  the  second  case, 
it  will  be  for  a  brief  period  from  left  to  right,  and  eventually  from 
right  to  left.  The  experiment  affords  the  general  condition  illustrated  by 
the  straight  and  bent  muscle  strips  of  Figure  IB  and  D.  The  result 
of  this  experiment  is  instructive.  Stimulate  the  epicardial  surface  and, 
from  the  first,  contact  Z  is  negative  to  contact  C.  This  finding  is  con- 
sistent with  both  hypotheses,  the  potentials  being  distributed  as  shown 
in  Figure  3  B  and  in  Figure  4.4  Stimulate  the  endocardial  surface 
(Fig.  3  C  and  D)  and  the  curve  has  two  opposite  phases,  a  short  first 
phase  during  which  contact  C  is  negative  to  contact  Z,  and  a  longer  sec- 
ond phase  during  which  contact  Z  is  negative  to  contact  C  (Fig.  4). 
This  finding  is  consistent  with  one  of  our  hypothesis  only,  namely, 
that  of  limited  potential  differences.  The  association  between  the  set 
of  the  current  and  the  direction  in  which  the  excitation  wave  moves 
will  be  noted  in  this  illustration.  It  constitutes  a  single  and  new  illustra- 
tion of  an  association  which  I  believe  to  be  firmly  established  and  of 
which  numeious  examples  have  already  been  published.5  It  was  because 
I  found  this  association  constantly  to  exist  in  the  normal  heart  beat  of 
amphibians,  reptiles,  birds  and  mammalia,  classes  in  which  the  spread 
of  the  excitation  wave  is  very  diverse,  that  I  first  recognized  the 
hypothesis  of  distributed  potentials  to  be  untenable,  for  it  is  incon- 
sistent with  this  association,  as  the  diagrams  clearly  show  (Figs.  3 
Cand  D). 

It  may  suffice  at  the  present  time  if  a  few  of  the  simpler  illustrations 
are  cited.  The  first  of  these  permits  the  display  of  some  important 
fallacies.  It  is  the  instance  of  the  normal  amphibian  heart  beat.  The 
amphibian  heart  ( Fig.  5 )  comprises  not  only  sinus,  auricle  and  ventricle, 
but  also  a  bulbus  arteriosus.  It  is  on  hearts  of  this  or  of  a  closely  allied 
type,  that  almost  the  whole  of  the  preliminary  explanations  of  the 
electrocardiogram  have  been  based ;  and  it  is  with  the  mistaken  inter- 
pretation of  these  curves,  and  the  hypotheses  derived  from  them,  that 
we  have  today  chiefly  to  contend.  In  this  early  work  the  heart  was 
examined  by  placing  on  the  base  and  apex  of  the  ventricle  two  contacts 
and  connecting  them  to  a  galvanometer.  Because  in  such  curves  as  were 
regarded  to  be  typical,  the  first  deflection  indicated  relative  negativity  of 
the  base,  it  was  concluded  that  the  base  first  becomes  active ;  it  was 
further  concluded  that  the  excitation  wave  spreads  as  a  simple  wave 
from  base  to  apex.  Now,  further  and  closer  observation  by  modern 


4.  In  stimulating  the  epicardial  surface  the  curve  is  not  usually  expressed 
as  a  single  phase.    It  rises  a  little,  hangs  or  falls  away  as  the  endocardial  lining 
is  approached,  and  then  rises  steeply  to  yield  the  chief  deflection  which  repre- 
sents rapid  involvement  of  a  large  mass  of  the  ventricular  substance. 

5.  Phil.  Tr.  Roy.  Soc.,  B.  207:221,  1916. 


ELECTROCARDIOGRAM  15 

methods  has  shown  that  the  first  of  these  conclusions  is  usually  incor- 
rect, and  that  the  last  conclusion  is  never  true.  These  early  observations 
on  the  cold-blooded  heart  and  the  conclusions  derived  from  them  are 
open  to  serious  criticism.  The  direction  of  the  first  deflection  does  not, 
in  point  of  fact,  always  indicate  primary  negativity  of  the  base.  The 
direction  depends  largely  in  a  given  animal  on  the  point  chosen  at  the 
base  for  examination ;  there  is  also  much  variation  from  animal  to  ani- 
mal. Later  observations  have  shown  that  sometimes  a  basal  point  is 
active  before  the  apex;  sometimes  it  becomes  active  after  the  apex 
(Fig.  5)  ;  sometimes  certain  points  at  the  base  are  activated  before,  and 
certain  points  after,  the  apex.  In  all  cases  the  base  and  apex  are  acti- 
vated within  a  very  short  time  interval  of  each  other.  The  excitation 
first  reaches  the  surface  of  the  heart  at  neither  base  nor  apex,  it  reaches 


•osob 


Fig.  5.  —  Outline  diagrams  of  the  hearts  of  Bufo  vulgaris  major,  showing 
a  number  of  surface  readings  expressed  (in  decimal  points  of  a  second) 
to  the  beginning  of  R  in  an  axial  lead.  Toad  A,  an  unpublished  figure, 
showing  that  the  base  is  activated  earlier  than  the  apex.  Toad  E  (after  the 
original  figure)  showing  that  the  apex  is  activated  earlier  than  the  base.  In 
both  cases  the  central  region  of  the  ventral  surface  is  activated  earliest  of  all. 
In  the  axial  electrocardiogram  of  each  animal  the  chief  deflection  was  an 
upright  R;  in  the  case  of  toad  E,  the  electrocardiogram  also  showed  a  prominent 
S  wave. 

the  central  portions  of  the  ventricle  (Figs.  5  and  6  A)  and  races 
simultaneously  up  to  the  base  and  down  to  the  apex;  the  race  may  be 
won  in  one  other  direction ;  usually  it  is  won  at  the  apex.  It  is  easy  to 
understand  why  these  base-apex  curves  of  early  days  often  seemed  to 
indicate  primary  negativity  of  the  base.  The  extreme  base  does  become 
active  a  little  before  the  apex  in  some  amphibian  hearts,  though  that 
is  not  the  rule.  If  the  extreme  apex  is  chosen  for  one  contact,  and  a 
point  somewhat  removed  from  the  base  is  chosen  for  the  second,  and 
this  would  be  the  natural  tendency  8  of  experiment,  primary  negativity 


6.  The  tendency  being  to  allow  an  interval  of  lesser  or  greater  extent  between 
the  contact  and  the  A-V  junction. 


16  SIR    THOMAS    LEWIS 

of  the  base  would  usually  be  manifested;  for  the  reason  that  a  point 
a  little  removed  from  the  base  is  usually  activated  earlier  than  a  point 
at  the  extreme  apex.  The  precise  time  relations  of  basal  and  apical 
activity  being  unknown  beforehand,  this  observation  would  naturally 
be  construed  as  indicating  that  the  excitation  wave  starts  at  the  base. 
From  this  conclusion,  false  as  it  was,  it  was  an  easy  step  to  the  still  very 
prevalent  general  erroneous  assumption  that  when,  as  is  the  rule,  the 
basal  contact  of  an  indirect  lead  (method  of  Fig.  IB)  first  demon- 
strates negativity,  activity  is  confined  to  muscle  which  lies  nearer  to 
this  basal  contact  than  to  the  apical  one.  Thus,  in  human  electro- 
cardiography  it  has  frequently  been  assumed  that  R,  the  chief  deflection, 
is  essentially  a  basal  effect  and  that  ^  is  essentially  an  apical  effect ;  for 
R  represents  relative  negativity  of  the  basal  and  S  of.  the  apical  contact. 
Neither  conclusion  is  justified. 

These  assumptions,  erroneous  as  I  believe  them  to  be,  arise  chiefly 
from  the  idea  that  if  muscle  at  the  base  is  active,  the  basal  contact  will 
show  relative  negativity  and,  conversely,  that  if  the  apex  is  active,  the 
apical  contact  will  show  relative  negativity.  These  are  views  based  on 
the  hypothesis  of  distributed  potentials.  A  primary  basal  activity  may 
display  itself  in  relative  negativity  of  the  apical  contact  as  the  experi- 
ment illustrated  in  Figure  3A  clearly  indicates.  The  erroneous  assump- 
tions also  arise,  in  part,  because  the  base-apex  curve  of  the  amphibian, 
where  contacts  are  laid  directly  on  the  heart,  has  been  assumed  too 
rigidly  to  be  comparable  with  the  curves  from  outlying  contacts  such 
as  are  used  in  clinical  electrocardiography.  The  difference  between  the 
two  methods  is  that  in  the  first  the  curve  chiefly  expresses  the  potential 
differences  between  two  small  areas,  one  at  the  base  and  one  at  the 
apex;  while  in  the  clinical  method  the  lead  (when  axial)  is  from  the 
whole  of  the  basal  and  the  whole  of  the  apical  parts  of  the  heart ;  the 
clinical  curves  express  the  electrical  changes  in  the  entire  mass  of 
cardiac  muscle;  the  direct  leads  do  not.  The  two  methods  are  strictly 
speaking  incomparable  (compare  Figs.  1C  and  D  from  this  point  of 
view). 

The  axial  electrocardiogram  of  the  amphibian  heart  (Fig.  7),  in 
so  far  as  it  expresses  spread  of  the  excitation  wave,  consists  of  the 
following  deflections. 

1.  A  chief  and  primary  deflection  (R)  indicating  relative  negativity 
of  the  contact  beyond  the  base. 

2.  An  inconstant  second  deflection  (S)  indicating  relative  negativ- 
ity of  the  contact  beyond  the  apex. 

3.  A   deflection    (B),   occurring  at   a  late   phase   of   the   electro- 
cardiogram, corresponding  to  activation  of  the  bulbus  arteriosus,  and 
indicating  relative  negativity  of  the  apical  contact. 


ELECTROCARDIOGRA  M 


17 


Let  us  deal  briefly  with  the  last  deflection  first.  This  bulbus  deflec- 
tion is  due  to  the  activity  of.  muscle  lying  at  the  base  of  the  ventricle ; 
yet  its  direction  indicates  relative  negativity  of  the  apical  contact.  This 
observation  clearly  warns  us  against  lightly  concluding  that  relative 


flid-|>liase. 


Fig.  6. — Course   of  excitation  wave   in  activation  of  ventricle. 


negativity  at  the  apical  contact  necessarily  means  activity  of  the  muscle 
lying  nearer  to  the  base  than  the  apex  of  the  ventricle.  The  direction  of 
this  deflection  is  what  it  is,  because  the  excitation  wave  begins  in  the 
lower  part  of  the  bulbus  (i.  e.,  toward  the  apical  contact)  and  the  inac- 
tive muscle  in  its  vicinity  lies  above  it  (i.  e.,  toward  the  basal  contact). 


18 


SIR    THOMAS    LEWIS 


The  position  of  the  bulbus,  relative  to  the  rest  of  the  ventricular  muscle 
with  which  it  is  in  functional  union  7  does  not  affect  the  direction  of  the 
deflection. 

Consider  now  the  initial  deflection  (7\?)  or  deflections  (R  and  S). 
The  meaning  of  R  according  to  my  hypothesis  is  not  obscure.  It  is 
due  to  set  of  the  current  in  the  axis  of  the  heart,  i.  c.  from  above  down- 
ward, over  the  greater  part  of  that  phase  of  the  cycle  during  which  the 
ventricle  is  becoming  activated.  The  ventricle  is  activated  in  the  gross 
from  above  downward.  The  excitation  wave  starts  in  the  muscular 
funnel  and  trabeculae  within  the  heart  (Fig.  6A)  and  is  at  first  prop- 
agated wholly  in  a  downward  direction.  Actually  the  greater  part 
or  entire  upstroke  of  R  is  written  before  the  excitation  wave  appears 
at  any  point  on  the  surface  of  the  ventricle.  To  regard  R  as  an  evi- 
dence of  general  basal  activity  is  obviously  inconsistent  with  this  obser- 
vation; R  corresponds  to  the  activity  of  muscle  lying  deep  inside  the 


Fig.  7. — An  electrocardiogram  taken  from  a  toad's  heart ;  leading  from  the 
mouth  and  abdomen  in  the  axis  of  the  heart.  The  deflection  produced  by  activity 
of  the  bulbus  arteriosus  (5)  is  directed  downward. 

central  portions  of  the  heart.  The  hypothesis  of  limited  potential  differ- 
ences applied  to  the  amphibian  ventricles  provides  us  with  a  clear  con- 
ception of  the  electrical  events,  a  conception  which  is  consistent  with 
the  manner  in  which  the  excitation  wave  has  been  shown  to  spread. 
During  the  early  phases  of  R's  inscription  the  muscle  is  becoming  active 
in  the  central  trabeculae,  this  region  is  relatively  negative,  the  relatively 
positive  region  lies  apexwards  and  in  its  immedate  vicinity  ( Fig  6B 
1st  phase).  As  the  excitation  wave  proceeds  downward,  the  advancing 
border  spreads  laterally,  but  the  balance  of  the  potential  differences 
manifests  itself  still  in  the  same  direction  (Fig.  6B  midphase).  In  its 


7.  The  reply  which  has  been  made,  that  there  is  a  natural  line  of  block 
between  the  two  chambers,  does  not  appear  to  me  relevant.  They  are  united  func- 
tionally by  muscle  fibers,  the  region  of  block  being  simply  a  region  of  slow  propa- 
gation; if  it  is  held  that  this  region  of  slow  propagation  constitutes  a  line  of 
complete  separation  from  the  standpoint  under  consideration,  the  burden  of 
proving  this  lies  with  those  who  hold  the  view. 


ELECTROCARDIOGRA  M 


19 


further  progress  the  advancing  border  of  the  wave  is  not  only  proceed- 
ing toward  the  apex,  but  is  now  also  traveling  back  in  the  lateral  walls 
to  reach  the  base  (Fig.  6B  end-phase  left-hand  figure).  Activity  in 
the  region  of  the  apex  still  tends  to  maintain  the  electric  axis 
from  base  to  apex ;  the  basal  activity  tends  to  set  it  in  a  contrary  direc- 
tion. But  the  effect  of  this  basal  activity  is  apparently  insufficient 
to  upset  the  average  direction,  which  still  remains  from  base  to  apex. 
The  basal  contact  is  throughout  relatively  negative  to  the  apical  contact. 
If,  however,  as  often  happens  in  the  amphibian  heart,  the  basal  seg- 
ments of  muscle  are  the  last  supplied,  this  opposition  of  the  apical 
effects  is  removed  and  the  effect  of  basal  activity  then  appears  It 
manifests  itself  in  the  form  of  an  6"  wave,  a  downward  deflection 
indicating  relative  negativity  of  the  apical  contact.  The  axis  of  the 
electromotive  force  is  now  from  below  upward  (Fig.  6B  end  phase, 
right-hand  figure). 


03-5- 


•ow 


OZ.5" 


•ozso 


Fig.  8. — Tim'es  of  arrival  of  excitation  wave  relative  to  each  other  indicated 
in  decimal  points  of  a  second. 

Thus,  our  hypothesis  brings  us  to  a  reasonable  explanation  of  a 
curious  but  actual  observation,  namely,  that  the  appearance  of  an  5 
wave  in  the  electrocardiogram  of  amphibians  is  associated  with  late 
arrival  of  the  excitation  wave  at  the  ventricular  base.  No  other  present 
day  hypothesis  will  afford  an  explanation  of  this  phenomenon.  This 
example  is  in  my  view  precisely  comparable  to  that  of  the  bulbus 
already  cited.  In  both  instances  basal  activities  are  responsible  for 
relative  negativity  of  the  apical  contact ;  but  the  present  illustration  has 
an  advantage  over  the  first,  in  that  there  can  be  no  question  here  of 
separate  muscle  systems ;  the  whole  of  the  musculature  of  the  ventricle 
is  one  uniform  syncytium. 

THE     MAMMALIAN     ELECTROCARDIOGRAM 

Similar  methods  of  observation  are  applied  to  the  mammalian  ven- 
tricle and,  although  in  this  instance  we  deal  with  a  far  more  complex 
arrangement,  similar  correlations  can  be  shown  to  exist  between  the 
manner  in  which  the  excitation  wave  spreads  and  the  set  of  the  elec- 


20  SIR    THOMAS    LEWIS 

trical  axis  from  instant  to  instant.  To  consider  the  constitution  of  this 
electrocardiogram  in  full  detail  would  detain  us  too  long,  it  must  suffice 
if  by  a  single  example  I  illustrate  again  the  general  principle  of  inter- 
pretation, and  show  that  the  hypothesis  of  limited  potential  differences 
is  applicable  in  this  case  also.  Let  us  take  the  simpler  case,  the 
excitation  of  the  dog's  left  ventricle. 

The  excitation  wave  is  found  by  observation  to  start  in  the  septum 
of  the  ventricles ;  it  is  traced  down  the  septum  to  the  apex  and  from  the 
latter  up  the  lateral  wall  to  the  base.  The  times  of  arrival,  relative  to 
each  other,  are  indicated  in  Figure  8  in  decimal  points  of  a  second. 
But  in  moving  along  this  semicircular  path  the  wave  does  not  proceed 
in  a  direction  parallel  to  the  borders  of  the  muscular  track,  it  is  pene- 
trating the  wall  in  successive  segments  of  its  course;  it  moves  always 
from  within  outward  along  centrifugal  paths;  each  part  of  the  wave 
travels  from  the  endocardial  to  the  pericardial  surface.  Throughout  its 
passage,  the  electrical  axis  constantly  changes  so  that,  while  in  the 
initial  stages  this  axis  sits  from  left  to  right  in  the  body,  it  gradually 
shifts  to  a  base-apex  direction ;  from  this  it  swings  more  and  more  to 
the  left  until,  eventually,  and  when  the  excitation  wave  is  reach- 
ing the  base  of  the  left  ventricle,  the  electrical  axis  is  directed 
chiefly  upward.  This  change  in  the  direction  of  the  axis  is 
responsible  for  the  complexity  of  the  corresponding  electrocardio- 
graphic  curves.  When  the  set  of  the  axis  is  in  the  main  down- 
ward, a  basal  contact  (right  shoulder)  is  relatively  negative  to  an 
apical  contact  (left  thigh)  ;  the  corresponding  upstroke  in  the  electro- 
cardiogram contributes  to  the  formation  of  the  well-known  deflection 
R.  On  the  contrary,  when  the  set  of  the  axis  is  mainly  upward,  the 
apical  contact  becomes  relatively  negative  to  the  basal  contact  and  the 
corresponding  downstroke  in  the  electrocardiogram  is  the  chief  constit- 
uent of  the  well  known  deflection  6".  As  in  the  amphibian  heart,  5  does 
not  represent  an  apical  activity,  it  represents  a  basal  activity.  Now  this 
example,  though  complex,  is  a  striking  one.  There  is,  within  the 
reasonable  bounds  of  error  in  observation,  complete  correspondence 
between  the  readings  which  indicate  the  distribution  of  the  advancing 
excitation  wave  and  the  set  of  the  electrical  axis  at  corresponding 
phases  of  the  cycle,  when  the  set  of  this  axis  is  read  in  terms  of  my 
hypothesis  of  limited  potential  differences.  These  observations  are  in 
full  accord  with  our  knowledge  of  the  anatomy  of  the  ventricle,  in 
accord  with  a  distribution  of  the  excitation  wave  through  the  left  divi- 
sion of  the  auriculoventricular  bundle  and  its  arborization ;  for  the  left 
division  enters  the  ventricle  on  its  septal  surface  and  distributes  its 
branches  to  the  septum,  to  the  apical  parts  of  the  heart  and  to  the 
lateral  walls  of  the  heart  and  to  the  lateral  walls  at  the  base,  in  this 
order.  Consider  the  ascertained  order  of  spread  and  arrange  theoreti- 


ELECTROCARDIOGRAM  21 

cally  the  electrical  axis,  using  the  hypothesis  of  distributed  potential 
differences,  and  one  arrives  at  a  result  which  is  not  consistent  with 
observation.  According  to  this  hypothesis,  relative  negativity  should 
appear,  first  of  all,  at  the  basal  contact ;  secondly  when  the  wave  of 
excitation  reaches  the  apex,  the  apical  contact  should  appear  relatively 
negative ;  finally  when  the  wave  returns  to  the  base,  the  basal  contact 
should  again  show  relative  negativity.  The  second  and  last  suppositions 
are  not  in  accord  with  the  facts.  But  if,  on  the  other  hand,  one 
arranges  the  potentials  theoretically,  using  the  hypothesis  of  limited 
potential  differences,  harmony  exists. 

In  the  light  of  these  observations  and  in  the  light  of  those  previously 
described,  I  have  no  hesitation  in  discarding  the  older  hypothesis  and  in 
accepting  in  its  place  the  hypothesis  which  I  term  that  of  limited 
potential  differences.  It  is  in  accord,  so  far  as  can  be  seen,  with  all 
present  observations  on  heart  muscle.  I  do  not  claim  that  it  affords 
a  final  explanation,  being  quite  prepared  to  find  that  future  observations 
will  necessitate  its  modification;  but  it  is  desirable,  nay  it  is  essential, 
that  we  should  possess  ourselves  of  an  hypothesis  which  harmonizes 
with  all  present  day  observation;  an  hypothesis  which  will  serve  to 
direct  further  experiment  along  fruitful  channels.  Hypotheses  which 
are  out  of  harmony  with  present  observations  will  not  serve  this  pur- 
pose. The  present  hypothesis  has  been  put  forward  and  is  now  empha- 
sized in  the  belief  that  it  will  supply  our  present  and  immediate  needs. 


Reprinted  from  the  Archives  of  Internal  Medicine 
September  15,  1922.  Vol.  30,  pp.  269-285 


COPYRIGHT,  1922 

AMERICAN   MEDICAL  ASSOCIATION 

FIVE   HUNDRED  AND   THIRTY-FIVE  NORTH   DEARBORN   STREET 
CHICAGO 


v*r^ 


